Cyclic-alkyl isothiuronium halides



Patented June 6, 1950 2,510,739 CYCLIC-ALKYL ISOTHIURONIUM HALIDES Le Roy W. Clemence, Highland Park, and Marlin T. Lcffler, Lake Bluff, Ill., assignors to Abbott Laboratories, North Chicago,

of Illinois 111., a corporation No Drawing. Application August 9, 1947, Serial No. 767,858

4 Claims.

The present application is a continuation-inpart of our prior application, Serial No. 723,907, filed January 23, 1947, which relates to oil soluble antimonials, and more specifically to tri-(substituted-mercapto) -antimonous acids.

The present application relates to novel compounds adaptable for use as intermediates in the preparation of the oil soluble antimonials of our prior application. More specifically, the present invention relates to w-cyclic-alkyl isothiuronium halides.

Among cyclic alkyl compounds which have been prepared are those with the alkyl chain having from one to ten carbon atoms. The preferred range of compounds includes those having from one to five carbon atoms because the compounds are relatively easier to prepare.

The compounds used a intermediates in the synthesis of tri[w-cyclohexylamylmercaptol-S- antimonous acid, trilw (B tetralyl) butyl mercaptol-Seantimonous acid and trilw-decalylbutyl-mercaptol -S-antimonous acid described in our prior application are new in the art and have been prepared by the methods given below.

In general, the w-cyclic-alkyl alcohol is converted to the w-cyclic alkyl halide by means of a phosphorous halide or a hydrohaloge'n acid. This halide is reacted with thiourea to form the w-cyclic-alkyl isothiuronium halide.

In detail, these compounds may be prepared as follows:

EXAMPLE 1 w-Gllclohexylamyl bromide CH1(0H1): CHaBr About 227 gms. (1.33 mole) of cyclohexylamyl alcohol (prepared by the hydrogenation of ethylw-cyclohexyl valerate at a temperature of 250" C. under a pressure of 3,600 pounds per square inch using a copper chromite catalyst. This alcohol 2 overnight it is heated to C. for several hours. The mixture is then cooled and poured into 1,000 cc. of ice and water with agitation. The heavy, oily layer is separated and dissolved in ether. the ether solution is Washed several times with water followed by a solution of sodium carbonate. After being rewashed with water, the ether solution isdried over magnesium sulfate, the magnesium sulfate is removed by filtration, and the ether evaporated. When fractionated in vacuum the yield obtained boils between 89.5-90.5 C. at 1 mm. pressure.

EXAMPLE II w-c'yclohemylamyl isothiuronium bromide To about 23.3 gms. (0.1 mole) of w-cyclohexylamyl bromide (Example I) is added a hot filtered solution of 7.6 gms. (0.1 mole) of thiourea in cc. of absolute alcohol containing a small amount of benzene as the denaturant (12A absolute alcohol). The mixture is refluxed for 36 hours, cooled, and stirred until the whole mass becomes a .crystalline mush. The solid is filtered, washed with a little acetone and dried. After recrystallization this material from boiling water, the compound has a melting point of Mil-141 C.

EXAMIPLE III w-(p-Tetralyl) -butyl bromide In a manner analogous to that of Example I but substituting w-(p-tetralyl) butyl alcohol (prepared by'hydrogenating ethyl w-(tetralyl) butyrate. This alcohol has a boiling point of 167 C. at 5 mm. and a refractive index of 1.5391 at 725 C. as compared to the D line of sodium) for w-cyclohexylamyl alcohol; the above mentioned compound is prepared. The w-(pg-tetralyl) butyl bromide obtained has a boiling point of 147-8 C. at 1 mm. pressure and a refractive index of 1.5528 at 25 C. when compared to the D line of sodium.

EXAMPLE IV w-Decalylbutyl bromide H CH2(CH:)2OH2BI H:

H: H Hi In a manner analogous to Example I but substituting w-decalylbutyl alcohol (prepared by hydrogenating ethyl w-decalylbutyrate. This alcohol has a boiling point f 148-9 C. at 0.5 mm. pressure and a refractiveindex of 1.4919 at 25 C. when compared to the D line of sodium) for a w-cyclohexylamyl alcohol; the above mentioned compound is obtained. This w-decalylbutyl bromide has a boiling point of 121-3 C. and a refractive index of 1.5020 at 25 C. when compared to the D line of sodium.

EXAMPLE V w- (p-Tetralyl) -butyl isothzuronium bromide Ha NH CH2(OH2)2GH2S(UJ"HBI EXAMPLE VI w-Decalylbutyl isothiurom'um bromide NH on oHoioHis-t t-Hm l IHa H Ha HBH H2 By substituting w-decalyl-butyl bromide (EX- ample IV) for w-cyclohexylamyl bromide in EX- ample II and proceeding as in that example, the compound w-decalylbutyl isothiuronium bromide is obtained. This compound has a melting point of 123-124 C.

The references to the term halogen is intended to includethe elements: chlorine, bromine, and. iodine.

Others may readily adopt the invention for use under varying conditions of service, by employing one or more of the novel features disclosed, or equivalents thereof. As at present advised with respect to the apparent scope of our invention, we desire to claim the following subject matter.

We claim:

1. A w-cyclic-alkyl isothiuronium halide with the formula:

wherein Y is selected from the group consisting of cyclohexyl, tetralyl and decalyl, R is a lower alkylene group containing from one to ten carbon atoms and X is a halogen atom.

2. The compound w-cyclohexylamyl isothiuronium bromide with the formula:

5 H fi H2 cmwmnom-s-o-msr NHz Hz HQ 3. The compound w-(B-tetralyl) -buty1 isothiuronium bromide with the formula:

Hg IIQ'H H2 CHa(CHz):CH2-S-A'HBI NH: H2

H2 4. The compound w-decalylbutyl isothiuronium bromide with the formula:

I vH H H OHz(CH2)2CHzS-C-HB1 H NH; H H:

g H Hi LE ROY W. CLEMENCE.

MARLIN T. LEFFLER.

REFERENCES CITED The following references are of record in the file of this patent:

UNITED STATES PATENTS Number Name Date 1,561,535 Hahl Nov. 17, 1925 2,147,346 Johnson Feb. 14, 1939 2,226,530 Brown et a1 Dec. 31, 1940 2,229,992 Schmidt Jan. 28, 1941 2,270,893 Orthner et a1 Jan. 27, 1942 2,302,885 Orthner et a1. Nov. 24, 1942 2 ,338,178 Graenacher Jan. 4, 1944 2,390,046 Albrecht Dec. 4, 1945 FOREIGN PATENTS 0 Number Country Date 215,036 Switzerland Aug. 16, 1941 226,819 Switzerland Aug. 2, 1943 OTHER REFERENCES Lecher: Liebigs Annalen, vol. 445 (1925) p. 39.

Donleavy: J Am. Chem. $00., vol. 58 (1936), pp.1004 and 1005.

Johnson et a1.: J. Am. Chem. 800., vol. 58 GO (1936), pp. 1348-1352.

Sprague et al.: J. Am. Chem. Soc., vol. 59 (1937), DD. 1837-1840.

Sprague et al.: J. Am. Chem. Soc, vol. 59 (1937), pp. 2439-2441.

Levy et a1.: J. Chem. Soc. (London), 1939, pp. 1442 to 1446.

Milley et al.: J. Am. Chem. Soc., vol. 62 (1940), pp. 2099-2102.

Wood et al.: J. Am. Chem. Soc.," vol. 62 (1940) 70 pp. 2674-2681.

Sprague et al.: J. Am. Chem. Soc.," vol. 68 (1946), pp. 2155-2159. 

1. A W-CYCLIC-ALKYKL ISOTHIURONIUM HALIDE WITH THE FORMULA: 